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Autoimmune RNA dysregulation and seizures: therapeutic prospects in neuropsychiatric lupus

Lupus autoimmunity frequently presents with neuropsychiatric manifestations, but underlying etiology remains poorly understood. Human brain cytoplasmic 200 RNA (BC200 RNA) is a translational regulator in neuronal synapto-dendritic domains. Here, we show that a BC200 guanosine-adenosine dendritic tra...

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Autores principales: Muslimov, Ilham A, Berardi, Valerio, Stephenson, Stacy, Ginzler, Ellen M, Hanly, John G, Tiedge, Henri
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Life Science Alliance LLC 2022
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9559755/
https://www.ncbi.nlm.nih.gov/pubmed/36229064
http://dx.doi.org/10.26508/lsa.202201496
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author Muslimov, Ilham A
Berardi, Valerio
Stephenson, Stacy
Ginzler, Ellen M
Hanly, John G
Tiedge, Henri
author_facet Muslimov, Ilham A
Berardi, Valerio
Stephenson, Stacy
Ginzler, Ellen M
Hanly, John G
Tiedge, Henri
author_sort Muslimov, Ilham A
collection PubMed
description Lupus autoimmunity frequently presents with neuropsychiatric manifestations, but underlying etiology remains poorly understood. Human brain cytoplasmic 200 RNA (BC200 RNA) is a translational regulator in neuronal synapto-dendritic domains. Here, we show that a BC200 guanosine-adenosine dendritic transport motif is recognized by autoantibodies from a subset of neuropsychiatric lupus patients. These autoantibodies impact BC200 functionality by quasi irreversibly displacing two RNA transport factors from the guanosine-adenosine transport motif. Such anti-BC autoantibodies, which can gain access to brains of neuropsychiatric lupus patients, give rise to clinical manifestations including seizures. To establish causality, naive mice with a permeabilized blood–brain barrier were injected with anti-BC autoantibodies from lupus patients with seizures. Animals so injected developed seizure susceptibility with high mortality. Seizure activity was entirely precluded when animals were injected with lupus anti-BC autoantibodies together with BC200 decoy autoantigen. Seizures are a common clinical manifestation in neuropsychiatric lupus, and our work identifies anti-BC autoantibody activity as a mechanistic cause. The results demonstrate potential utility of BC200 decoys for autoantibody-specific therapeutic interventions in neuropsychiatric lupus.
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spelling pubmed-95597552022-10-14 Autoimmune RNA dysregulation and seizures: therapeutic prospects in neuropsychiatric lupus Muslimov, Ilham A Berardi, Valerio Stephenson, Stacy Ginzler, Ellen M Hanly, John G Tiedge, Henri Life Sci Alliance Research Articles Lupus autoimmunity frequently presents with neuropsychiatric manifestations, but underlying etiology remains poorly understood. Human brain cytoplasmic 200 RNA (BC200 RNA) is a translational regulator in neuronal synapto-dendritic domains. Here, we show that a BC200 guanosine-adenosine dendritic transport motif is recognized by autoantibodies from a subset of neuropsychiatric lupus patients. These autoantibodies impact BC200 functionality by quasi irreversibly displacing two RNA transport factors from the guanosine-adenosine transport motif. Such anti-BC autoantibodies, which can gain access to brains of neuropsychiatric lupus patients, give rise to clinical manifestations including seizures. To establish causality, naive mice with a permeabilized blood–brain barrier were injected with anti-BC autoantibodies from lupus patients with seizures. Animals so injected developed seizure susceptibility with high mortality. Seizure activity was entirely precluded when animals were injected with lupus anti-BC autoantibodies together with BC200 decoy autoantigen. Seizures are a common clinical manifestation in neuropsychiatric lupus, and our work identifies anti-BC autoantibody activity as a mechanistic cause. The results demonstrate potential utility of BC200 decoys for autoantibody-specific therapeutic interventions in neuropsychiatric lupus. Life Science Alliance LLC 2022-10-13 /pmc/articles/PMC9559755/ /pubmed/36229064 http://dx.doi.org/10.26508/lsa.202201496 Text en © 2022 Muslimov et al. https://creativecommons.org/licenses/by/4.0/This article is available under a Creative Commons License (Attribution 4.0 International, as described at https://creativecommons.org/licenses/by/4.0/).
spellingShingle Research Articles
Muslimov, Ilham A
Berardi, Valerio
Stephenson, Stacy
Ginzler, Ellen M
Hanly, John G
Tiedge, Henri
Autoimmune RNA dysregulation and seizures: therapeutic prospects in neuropsychiatric lupus
title Autoimmune RNA dysregulation and seizures: therapeutic prospects in neuropsychiatric lupus
title_full Autoimmune RNA dysregulation and seizures: therapeutic prospects in neuropsychiatric lupus
title_fullStr Autoimmune RNA dysregulation and seizures: therapeutic prospects in neuropsychiatric lupus
title_full_unstemmed Autoimmune RNA dysregulation and seizures: therapeutic prospects in neuropsychiatric lupus
title_short Autoimmune RNA dysregulation and seizures: therapeutic prospects in neuropsychiatric lupus
title_sort autoimmune rna dysregulation and seizures: therapeutic prospects in neuropsychiatric lupus
topic Research Articles
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9559755/
https://www.ncbi.nlm.nih.gov/pubmed/36229064
http://dx.doi.org/10.26508/lsa.202201496
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